title: High fat diet reduces the expression of glutathione peroxidase 3 in mouse prostate.
abstract: BACKGROUND
  High fat diets are known to be a risk factor for prostate cancer. In this study, we investigated the effect of high fat diet on mouse prostate gene expression.
  
  
  METHODS
  C57BL/6J mice were fed either a control or high fat diet for 12 weeks. Microarray analyses were performed on mouse ventral prostate (VP) and dorsolateral prostate (DLP), followed by canonical pathway analysis and regulatory network identification. mRNA changes were confirmed by real time PCR.
  
  
  RESULTS
  Approximately 2,125, and 1,194 genes responded significantly to the high fat diet in VP, DLP, respectively. Pathways and networks related to oxidative stress, glutathione metabolism, NRF-mediated oxidative stress response and NF-kappaB were all differentially regulated by high fat diet. Glutathione peroxidase 3 (GPx3) mRNA levels were decreased by approximately twofold by high fat diet in all three prostate lobes. In human non-transformed prostate cells (PrSC, PrEC, and BPH-1), cholesterol loading decreased GPx3 expression, and increased H2 O2 levels of culture medium. Troglitazone increased GPx3 expression in three normal prostate cells, and decreased H2 O2 levels. In addition, troglitazone attenuated cholesterol-induced H2 O2 increase. Tissue from prostate cancer biopsies had decreased GPx3 mRNA and its level was inversely related to the Gleason score.
  
  
  CONCLUSIONS
  High fat diet alters pathways related to many genes concerned with oxidative stress. GPx3, a gene identified by this analysis, was found to be down-regulated by high fat diet and appears be decreased in human prostate cancers, suggesting that GPx3 may have a possible role in modulating carcinogenesis. Prostate 71:1499-1509, 2011. © 2011 Wiley-Liss, Inc.
authors.affiliation: Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland; Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. ysekine@showa.gunma-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekine
authors.forename: David
authors.initials: D
authors.lastname: Osei-Hwedieh
authors.forename: Kant
authors.initials: K
authors.lastname: Matsuda
authors.forename: Nalini
authors.initials: N
authors.lastname: Raghavachari
authors.forename: Delong
authors.initials: D
authors.lastname: Liu
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Furuya
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Koike
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
mesh_terms: D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D059305:Diet, High-Fat; D004847:Epithelial Cells / Q000166:cytology; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000502:physiology; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000502:physiology; D011467:Prostate / Q000166:cytology / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D017154:Stromal Cells / Q000166:cytology; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D002839:Chromans; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D045162:Thiazolidinediones; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; D000077288:Troglitazone